On September 23, 2019 Flagship Pioneering, a unique life science innovation enterprise, reported that it unveiled Omega Therapeutics – a genomics medicine company focused on selectively directing the human genome to treat and cure disease by precisely controlling genomic expression without changing nucleic acid sequences (Press release, Omega Therapeutics, SEP 23, 2019, View Source [SID1234561269]). Mahesh Karande has been appointed as the company’s President, CEO and member of the Board of Directors. Mr. Karande was the former President and CEO of Macrolide Pharmaceuticals and a long-time Novartis AG executive where he held positions of increasing responsibility running large businesses in the U.S. and internationally. Flagship Pioneering developed and launched Omega Therapeutics through its innovation foundry, Flagship Labs.

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Since its founding in 2017, under the leadership of David Berry, M.D., Ph.D., General Partner of Flagship Pioneering, Omega Therapeutics has created a proprietary platform that precisely tunes Insulated Genomic Domains (IGDs), the fundamental regulator, or GenomStats, of the human genome, which are 3D closed-loop structures of DNA that control genomic activity, to unlock the native power of the genome to cure diseases. This enables the unique, rapid development of specific therapeutics that treat disease and help patients, without altering nucleic acid sequences, with implications across a variety of indications. Engineered genomic modulators, called Omega Controllers, precisely tune genomic activity to desired therapeutic levels to address the biological root of disease. Our therapeutics are designed to be more specific and durable and, as such, potentially more effective therapeutic options for patients.

"By mapping the topology of the human genome and using computational biology, we have been able to identify the correct genomic target for a therapeutic influence. Omega’s proprietary platform technology allows us to develop therapeutics for disease control, and potentially impact the way we treat and manage a broad range of illnesses," said Dr. Berry. "In addition to our own capabilities for therapeutic development, our technology also presents the opportunity to partner and optimize other targeted in vivo and ex vivo therapeutics to enhance their ability to treat disease and further help a wide range of patient populations with significant unmet needs."

Many health conditions, particularly complex diseases, are the result of malfunctions in the regulation of gene expression. Omega leverages the founding Flagship team’s pioneering innovations that extended the breakthrough work on epigenetics by Richard Young, Ph.D., Professor of Biology, Massachusetts Institute of Technology, and Member of the Whitehead Institute, and Rudolf Jaenisch, M.D., Professor of Biology, Massachusetts Institute of Technology and Founding Member of the Whitehead Institute, who first described how genomic activity is controlled by 3D closed-loop structures of DNA, now called Insulated Genomic Domains (IGDs), that contain one or more genes and their regulatory elements.

These insulated, or closed-loop, structures ensure that interaction between the regulatory elements and gene(s) leading to gene expression is contained within the IGD. Diseases often manifest due to alterations in gene expression or changes in IGD structure. As such, the IGD is the fundamental regulator, or GenomStat, of the human genome. Omega is pioneering the discovery and development of precision Omega Controllers to control the GenomStat. By precisely tuning the GenomStat, Omega Controllers regulate single- or multi-gene expressions to desired levels to treat or cure disease. Scientific strategy and research and development will be led by Chief Science Officer, Thomas McCauley, Ph.D., former Shire executive and more recently CSO of Macrolide Pharmaceuticals and CSO of Translate Bio (formerly RaNA Therapeutics).

"Flagship is focused on discovering value and innovating well beyond the boundaries of current research in order to build first-of-their-kind companies. Omega’s proprietary product-platform is taking an entirely new approach to tackling important, unsolved diseases," said Noubar Afeyan, Ph.D., Chief Executive Officer of Flagship Pioneering and Chair of Omega’s Board of Directors. "The executive team, board of directors and scientific advisors have created an unparalleled company that fits the extraordinary scope of the therapeutic potential of Omega Controllers, a new class of medicines."

"The depth and breadth of our platform gives us the ability to create transformative genomic medicines that deliver specificity of targeting, tunability, and durability of single and multi-gene expression, all without altering nucleic acid sequences. Our platform enables us to develop proprietary Omega Controllers, a new class of therapeutics targeting the control of a wide range of diseases in unprecedented ways," said Mr. Karande. "With a team of world-class scientists, founders and advisors, we are already executing several ambitious early-stage discovery programs in the near-term, as we strengthen our platform to address the vast opportunity of treating diseases resulting from genomic malfunction or dysregulation."

Omega Therapeutics is targeting the biological root of disease and designing novel therapeutics and optimizing current therapies to potentially address a wide range of disease categories, including rare genetic diseases, immunology, inflammation, metabolic diseases and oncology.

The Omega Therapeutics Board of Directors:

– David Berry, M.D., Ph.D., General Partner, Flagship Pioneering, Co-founder, Omega Therapeutics

– Richard Young, Ph.D., Professor of Biology, Massachusetts Institute of Technology, Member, Whitehead Institute

– Paul-Peter Tak, M.D., Ph.D., Chief Executive Officer, Kintai Therapeutics, Venture Partner, Flagship Pioneering, former Senior Vice President and Global Head of R&D for Immuno-inflammation, Oncology and Infectious Disease, as well as Chief Immunology Officer, GlaxoSmithKline (GSK)

– Mary Szela, Chief Executive Officer, TriSalus Life Sciences, former Chief Executive Officer, Novelion Therapeutics, and Chief Executive Officer, Melinta Therapeutics

– Mahesh Karande, President and Chief Executive Officer, Omega Therapeutics

– Noubar Afeyan Ph.D., Co-founder and Chairman of the Board, Omega Therapeutics, CEO Flagship Pioneering

ABOUT MAHESH KARANDE, PRESIDENT AND CHIEF EXECUTIVE OFFICER

Mahesh Karande is deeply experienced in running biopharma businesses across discovery, preclinical development, clinical development, commercialization and product life-cycle management stages. He has strong leadership and operational experience combined with a global work history spanning the United States, Europe, Asia and Africa. Most recently, Mr. Karande, as President and CEO, took Macrolide Pharmaceuticals, from discovery into early development. Earlier, Mr. Karande spent several years at Novartis, leading various U.S. and international business units. Mr. Karande left Novartis to join Intarcia Therapeutics as VP and General Manager to lead the launch of their first product; a role he left to take the helm at Macrolide.

On September 23, 2019 Genprex recently reported that independent researchers found that company’s TUSC2 (tumor suppressor candidate 2) prevented tumor growth in triple-negative breast cancer (TNBC) (Press release, Genprex, SEP 23, 2019, View Source [SID1234551277]). These independent researchers have no affiliation with Genprex.

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Genprex takes a deeper dive into the data of the study to provide analysis and a better understanding of what the study found and what it means for TUSC2.

The study, "MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression," takes a look at one particular subtype of breast cancer, triple-negative breast cancer (TNBC).

Triple Negative Breast Cancer

According to the National Breast Cancer Foundation, TNBC occurs in about 10-20 percent of diagnosed breast cancers, and is more likely to affect younger patients (under the age of 50 years old), African Americans, Hispanics and those with a BRCA1 gene mutation.1,5

A diagnosis for TNCB means that the patient does not have any of the three most common types of receptors that enable breast cancer growth, including estrogen, progesterone and the HER2 gene, thus the name for triple-negative breast cancer.1 TNBC progresses rapidly and is more likely to metastasize to the brain and viscera relative to HER2+ cancers.5

Treating TNBC with today’s emerging targeted therapies and immunotherapies are typically ineffective because these receptors are not present. This makes TNBC difficult to treat, and as an aggressive cancer, it is increasingly a feared diagnosis. With few treatment options, most TNBC patients must undergo a lumpectomy, a mastectomy, radiation, chemotherapy or a combination of these treatments.2TNBC patients are significantly less likely to survive than other breast cancer patients following the first metastatic event.5

The Role of MicroRNA-138

MicroRNA, or miRNA, help to downregulate gene expression in a variety of manners.3Thousands of miRNAs have been identified, and miRNAs possess the capacity to target between tens and hundreds of genes simultaneously. They perform a key role in tumorigenesis as important modulators in cellular pathways by regulating target gene expression through translation repression or mRNA degradation.4

Increased miR-138 expression is highly specific to TNBC, and the Nature report notes that miR-138 correlates with poor prognosis in patients, and it is functionally relevant to cancer progression.

The independent researchers explored the role of miR-138 in TNCB and found that it is a specific molecular signature of TNBC and a prognostic biomarker for breast cancer pathogenesis. Researchers also found miR-138 to be a pro-survival oncomiR for TNBC, meaning that overexpression of the gene leads to cancerous tumor growth.6Lastly, when miR-138 is depleted, it leads to apoptotic cell death in vitroand prevents tumorigenesis in vivo. In finding a way to deplete miR-138, this could lead to cancer cell death.

The Role of TUSC2

The independent researchers also found that TUSC2, which is the active agent in Genprex’s lead drug candidate, was a direct target downregulated by miR-138. TUSC2 expression is elevated and TUSC2 protein levels are enhanced following miR-138 knockdown.In TNBC mouse model studies using TUSC2, tumors were barely detectable under miR-138 knockdown conditions, and the implantation of TUSC2 overexpressing cells yielded tumors that are significantly smaller than those in the control group. TUSC2 expression was found to substantially mimic miR-138 knockdown and prevent tumor growth, revealing a potential new treatment for TNBC.

On September 23, 2019 Mateon Therapeutics Inc. (OTCQB:MATN) reported that the US Food and Drug Administration (FDA) granted Rare Pediatric Disease Designation for OT101/Trabedersen for the treatment of diffuse intrinsic pontine glioma (DIPG) as a drug for a "rare pediatric disease (Press release, Mateon Therapeutics, SEP 23, 2019, View Source [SID1234539855])."

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"We are excited about this Rare Pediatric Disease designation for our lead anti-brain tumor drug candidate for pediatric DIPG patients who are in urgent need for therapeutic innovations," said Dr. Vuong Trieu, Chief Executive Officer of Mateon. "We will continue to build on our pipeline of therapeutics for rare and orphan diseases, including cancers."

Brainstem tumors comprise approximately 10-15 percent of all pediatric brain tumors and DIPG is the most common brainstem tumor and the second most common malignant brain tumor of childhood. DIPG, is an orphan disease with a low survival rate and no established or effective standard of care. Despite numerous clinical trials of chemotherapeutic agents, immuno-oncology drugs and specific targeted therapies, no significant progress has been made in the treatment of DIPG and the prognosis remains dismal, with a mean OS of 9–12 months from the time of diagnosis, a median survival time of approximately 10 months, and a two-year OS rate of less than 10 percent. Five-year survival is less than 3 percent, and many long-term survivors have evidence of moderate or severe cognitive impairment, likely as a consequence of radiation therapy. Chemotherapy does not have an established role in the management of patients with DIPG. Furthermore, there is no standard treatment for progressive DIPG after the failure of radiation therapy and no salvage regimen has been shown to extend survival. Therefore, there is an urgent need for therapeutic innovations for treatment of DIPG, as reflected by multiple treatment modalities being evaluated in early neuro-oncology clinical trials.

OT101, a first-in-class RNA therapeutic, is designed to abrogate the immunosuppressive actions of TGF-beta 2. In a completed Phase 2 clinical study, OT-101 exhibited clinically meaningful single-agent activity and induced durable complete and partial responses in recurrent and refractory adult high-grade glioma patients, including adults with GBM. Further development of OT-101 may offer renewed hope for salvage therapy of pediatric DIPG patients who have this rare and fatal disease.

The FDA grants rare pediatric disease designation for diseases with serious or life-threatening manifestations that primarily affect people aged from birth to 18 years, and that affect fewer than 200,000 people in the U.S. Under the FDA’s Rare Pediatric Disease Priority Review Voucher program, a sponsor who receives an approval of a new drug application or biologics license application for a product for the prevention or treatment of a rare pediatric disease may be eligible for a voucher, which can be redeemed to obtain priority review for any subsequent marketing application, and may be sold or transferred. In August 2019, AstraZeneca has reportedly paid approximately $95 million to buy a priority review voucher from Swedish Orphan Biovitrum (Sobi) (View Source). Likewise, Biohaven Pharmaceutical Holding Company Ltd. reportedly paid approximately $105 million for a priority review voucher in March 2019 (View Source).

Dr. Fatih Uckun, the Chief Medical Officer of Mateon is scheduled to give both a talk and a poster presentation on the clinical safety and anti-brain tumor efficacy of OT101 at the 24th Annual Meeting of the Society for NeuroOncology in Phoenix, Arizona in November 2019.

"The durable objective responses achieved in adult patients with recurrent/refractory high-grade gliomas after treatment with our lead anti-TGF beta2 compound OT-101 contribute to our optimism that new treatment strategies leveraging OT101 may favorably change the therapeutic landscape for difficult-to-treat brain tumors with a very poor prognosis," Dr. Uckun explained. "Our recent bioinformatics research has revealed that the TGF beta2 gene product, which is the molecular target for OT101, may serve as a target for immunotherapy in pediatric high-grade gliomas, especially DIPG. These in silico target validation data recently accepted for publication in a peer-reviewed medical journal extend the promising clinical data on the therapeutic activity of OT101 in adults and young adults and further demonstrate the potential of OT101 as a promising drug candidate in the treatment of pediatric DIPG, an orphan disease with a low survival rate and no established or effective standard of care."

Last month, Mateon announced that it had entered into a definitive agreement for the potential acquisition of PointR Data, Inc. (PointR), a privately-held developer of high-performance cluster-computing technologies for artificial intelligence. The proposed transaction would create a publicly-traded AI driven immuno-oncology company.

"We are working toward integrating artificial intelligence and drug development capabilities under one roof to create a pipeline of therapeutics for the niche market of rare pediatric diseases often ignored by large pharma" said Saran Saund, PointR’s Chief Executive Officer.

"AI-based cognitive technologies have the potential to streamline our clinical development strategy for the portfolio drug candidates by amplifying our knowledge and understanding of the target pediatric cancers, their biology as well as structural and pharmacologic characteristics of the lead compounds", said Dr. Fatih Uckun, MD, PhD, the Chief Medical Officer of Mateon. "Furthermore, the combined use of AI and the Blockchain technology supported by the PointR AI computing platform has a very high impact potential for a better cancer care and especially patient-tailored cancer treatments for pediatric and young adult cancer patient populations."

On September 23, 2019 Xynomic Pharmaceuticals Holdings, Inc. ("Xynomic", stock ticker: XYNO), a clinical stage US-China oncology drug development company, reported that the U.S. Food and Drug Administration ("FDA") has granted Fast-Track designation to Xynomic’s lead drug candidate abexinostat, for use as a single agent, as a fourth-line treatment of relapsed or refractory follicular lymphoma ("FL") (Press release, Xynomic Pharmaceuticals, SEP 23, 2019, View Source [SID1234539846]). Fast-Track is a designation by the FDA to facilitate the development and expedite the review of drugs to treat serious or life-threatening conditions and fill an unmet medical need.

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According to the U.S. National Cancer Institute, FL is the most common indolent non-Hodgkin’s lymphoma subtype in the U.S. with approximately 14,840 new cases per year. It often requires multiple lines of treatment. Despite current available therapies, the outlook for patients that fail third line FL treatment remains poor. The median PFS and EFS were both less than 1 year after third line of treatment. Xynomic is conducting a potentially pivotal Phase 2 trial of abexinostat, for use as a single agent, as a fourth-line treatment of relapsed or refractory FL in the U.S. and Europe.

FDA has already granted Fast-Track designation to abexinostat, in combination with pazopanib, as a first- or second-line treatment of renal cell carcinoma.

On September 23, 2019 Celsius Therapeutics, a company focused on bringing personalized medicine to patients with cancer, autoimmunity and other complex diseases, reported that it has been named by FierceBiotech as one of 2019’s Fierce 15 biotechnology companies, designating it as one of the most promising private biotechnology companies in the industry (Press release, Celsius Therapeutics, SEP 23, 2019, View Source [SID1234539743]).

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"It is an incredible honor and we are humbled to be named a ‘Fierce 15’ company, which is a testament to both our promising single cell genomics-driven drug discovery approach as well as the hard work of our entire team," said Tariq Kassum, M.D., chief executive officer of Celsius. "At Celsius, the combination of patient tissue samples, massive datasets, and sophisticated machine learning algorithms allows us, for the first time, to understand the specific cells driving disease. With this new level of clarity, our approach has fierce potential to deliver a powerful new class of precision medicines in autoimmune disease and cancer."

"This year has seen unrivalled scientific talent in the early-stage life sciences world and it has been a pleasure to for us at FierceBiotech to speak to all 15 winners and hear their passion, progress and panache," said Ben Adams, Senior Editor of FierceBiotech. "Each company brought something different, exciting and potentially life-changing for myriad patients around the world across a host of diseases and disorders, using cutting-edge science, top-notch teams and a drive to genuinely make the world a better place, despite the risks and challenges that, as ever in biotech, lay ahead."

The Fierce 15 celebrates the spirit of being "fierce" – championing innovation and creativity, even in the face of intense competition. Every year FierceBiotech evaluates hundreds of private companies from around the world for its annual Fierce 15 list, which is based on a variety of factors such as the strength of its technology, partnerships, venture backers and a competitive market position. This is FierceBiotech’s 17th annual Fierce 15 selection.